The vertebrate immune system is unique in that it is a spread out series of cells and tissue, instead of a concentrated single organ. In humans, there are about 10.sup.12 total cells in the system, including those of the spleen, liver, thymus, bone marrow, lymph nodes, and the circulating cells of the blood and lymph. Together, the cells have a mass of about 2 kilograms, which is about equivalent to that of an adult liver.
In general, the immune system protects an organism from disease by responding to disease causing antigens using a complicated mechanism which recognizes, inactivates, and destroys the antigen. To be effective, the immune system must first discriminate between potential antigens which are the molecules of the organism it serves to protect and actual antigens which are foreign invaders. The immune system must localize and destroy the foreign antigens, a process that involves not only antibodies and lymphocytes but also several plasma proteins that together form a defense mechanism called the complement system.
Interaction of the foreign antigens with components of the immune and complement systems stimulates the production of biologically active substances that amplify immunological recognition. These substances enhance local vascular permeability and vascular stasis and chemotactically attract phagocytic circulatory cells to the local sites of the immune reactions. These processes produce a localized inflammatory response and the recruited cells ingest the antigens.
The immune system, having interacted with a particular antigen, acquires an "immunity" to that specific antigen. Subsequent contact with the same antigen elicits a rapid stimulation of the immune system which quickly destroys the antigen before it can harm the organism. This "immunity" for a specific antigen can be produced by accidental contact with an antigen or can be induced by exposing the immune system to non-lethal doses of the antigen, components of an antigen, or to biologically inactive antigens.
The limitation inherent in the immune system is, however, its specificity. The immune system retains an "immunity" only for the specific antigens with which it has previously reacted. When the immune system first encounters a different antigen, it cannot respond as rapidly to the new invader as it could to a previously encountered antigen for which an immunity had been acquired. This leaves the organism succeptable to disease and other harmful effects caused by new invading antigens even though the immune system has an "immunity" against thousands of other specific antigens. The immune system, because of its specificity, has no method for acquiring an "immunity" against antigens as a general class. A method is therefore needed which can stimulate the immune system non-specifically and produce an effective "immunity" to antigens in general. The immune system could, therefore, rapidly destroy any antigen invading the organism. Such a method would enhance the immune system's ability to combat disease and increase the overall effectiveness of the vertebrate immune system.
Prior art methods for stimulating the immune system include: U.S. Pat. No. 4,420,481 to Okazaki et al discloses the use of piperazine compounds as immunostimulating agents for the treatment of arthritis and other immune system diseases. U.S. Pat. No. 4,281,120 to Herrling discloses using derivatives having immune stimulating properties for anti-infectious therapy in mammals, including man. U.S. Pat. No. 4,173,641 to Kraska discloses glycerol derivatives useful as non-specific stimulants of cell mediated immunity. U.S. Pat. No. 4,444,767 to Torelli et al discloses the use of 3-amino-pregen-5-ene derivatives as stimulants of the mammalian immune system. U.S. Pat. No. 4,571,336 to Houck et al discloses immunostimulating peptides useful for treating mammals and birds at risk from viral or fungal infections or other trauma.
Preparation of the immunostimulating RAL derivatives of the present invention, zearalenone, zearalanone, zearalene, zearalane, zearalenol, zearalanol, and dideoxyzearalane, are disclosed in U.S. Pat. Nos. 3,196,019, 3,239,354, 3,239,341, 3,239,348, 3,239,345, and 3,453,367, all incorporated herein by reference. Some of these compounds are used as growth promotants in animals.